Wieland Ivonne, Kentouche Karim, Jentzsch Madlen, Lothschütz Daniela, Graf Norbert, Sykora Karl-Walter
Department of Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany.
Pediatr Blood Cancer. 2015 May;62(5):823-9. doi: 10.1002/pbc.25398. Epub 2015 Jan 13.
Acquired thrombotic-thrombocytopenic purpura (TTP) is an autoimmune disorder characterized by autoantibodies directed against the von Willebrand metalloprotease. Depletion of B-cells can prevent synthesis of this antibody and presumably induce remission of the disease. In adults, Rituximab (RTX) was effective in relapsed or refractory acute idiopathic TTP.
We report the long-term follow-up of five children and two adolescents (age at diagnosis 6-19 years, median 15 years) who were treated with RTX for recurrent or refractory TTP. Some of the patients suffered from recurrent refractory TTP with long histories of previous unsuccessful treatments. One had TTP associated with pancreatitis.
Three patients have been in complete remission after one treatment course with RTX. Four relapsed after 1 to 5 years, respectively, and responded to additional courses of RTX. One of them is in long-term remission after a third course of RTX and splenectomy. Compared to literature reports with a median follow up of 1.4 years (3-46 month), follow-up of our patients after treatment with RTX was very long (2-12.7 years, median 7.7 years). RTX therapy could induce long-term remissions in children with refractory recurrent TTP. Median duration of remission was longer and relapses per patient-years less frequent in patients receiving RTX compared to patients not receiving it. Remissions were achieved in children within one week, much faster than in adults.
Because of the rapid induction of remissions, RTX may be suitable for first-line therapy in pediatric acquired antibody-mediated TTP.
获得性血栓性血小板减少性紫癜（TTP）是一种自身免疫性疾病，其特征是存在针对血管性血友病金属蛋白酶的自身抗体。B细胞的耗竭可阻止该抗体的合成，并可能诱导疾病缓解。在成人中，利妥昔单抗（RTX）对复发或难治性急性特发性TTP有效。
我们报告了5名儿童和2名青少年（诊断时年龄6 - 19岁，中位年龄15岁）接受RTX治疗复发性或难治性TTP的长期随访情况。部分患者患有复发性难治性TTP，既往有长期治疗失败史。1例患者的TTP与胰腺炎相关。
3例患者在接受一个疗程的RTX治疗后完全缓解。4例分别在1至5年后复发，并对额外疗程的RTX有反应。其中1例在接受第三个疗程的RTX和脾切除术后长期缓解。与中位随访时间为1.4年（3 - 46个月）的文献报道相比，我们的患者接受RTX治疗后的随访时间非常长（2 - 12.7年，中位7.7年）。RTX治疗可使难治性复发性TTP儿童获得长期缓解。与未接受RTX治疗的患者相比，接受RTX治疗的患者缓解期的中位持续时间更长，每患者年的复发频率更低。儿童在一周内即可实现缓解，比成人快得多。
由于能迅速诱导缓解，RTX可能适用于儿童获得性抗体介导的TTP的一线治疗。
